This four-year competing renewal application proposes to continue ongoing research on the toxicities associated with bone marrow transplantation (BMT) and to improve interventions for symptom control. Our broad research missions are to characterize the severe oral mucositis consequential to preparative chemoradiography and to improve methods for controlling the associated severe pain. The specific aims of this program project are to: 1) Quantify and profile oral pain and other regimen-related toxicities in BMT patients; 2) Undertake preclinical pharmacologic and psychologic research in the human studies laboratory that facilitates clinical interventions for pain; and 3) Improve pharmacologic and psychologic interventions for the pain of severe oral mucositis through clinical trials. This application is a multidisciplinary confederation of five interdependent projects and three core units. Project 1 is an intensive study of oral mucositis and related complications by an oral medicine team. Project 2 contains current work on pharmacologic control of oral pain by evaluating innovations in patient-controlled opioid analgesia. Project 3 refines and further evaluates cognitive-behavioral innovations for oral pain and symptom control. Project 4, conducted in a human studies laboratory, will define the analgesia-to-side-effect ratios for several agonist-antagonist and partial agonist opioid drugs that have potential benefits for cancer patients with pain. Project 5, also a human laboratory project, will investigate the analgesia obtained with epidurally administered opioids and compare selected drugs. The core units are: Administrative and General Services, Information Management (data and statistical services), and Pharmacology. The long-range research mission of this program project is to advance pharmacologic and behavioral methods for the control of pain and other symptoms in all cancer patients, including those with far advanced terminal disease. The innovations in pharmacologic and behavioral interventions developed for immediate application in the BMT setting have direct application for the control of pain in other patient populations.